Mechanism of a Novel Camptothecin-Deoxycholic Acid Derivate Induced Apoptosis against Human Liver Cancer HepG2 Cells and Human Colon Cancer HCT116 Cells

Author(s): Linxia Xiao, Jialin Xu, Qi Weng, Leilei Zhou, Mengke Wang, Miao Liu, Qingyong Li*.

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Volume 14 , Issue 4 , 2019

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Background: Camptothecin (CPT) is known as an anticancer drug in traditional Chinese medicine. However, due to the lack of targeting, low solubility, and instability of CPT, its therapeutic applications are hampered. Therefore, we synthesized a series of CPT-bile acid analogues that obtained a national patent to improve their tumour-targeting chemotherapeutic effects on liver or colon cancers. Among these analogues, the compound G2 shows high antitumor activity with enhanced liver targeting and improved oral absorption. It is significant to further investigate the possible anticancer mechanism of G2 for its further clinical research and application.

Objective: We aimed to unearth the anticancer mechanism of G2 in HepG2 and HCT116 cells.

Methods: Cell viability was measured using MTT assay; cell cycle, Mitochondrial Membrane Potential (MMP), and cell apoptosis were detected by flow cytometer; ROS was measured by Fluorescent Microplate Reader; the mRNA and protein levels of cell cycle-related and apoptosis-associated proteins were examined by RT-PCR and western blot, respectively.

Results: We found that G2 inhibited cells proliferation of HepG2 and HCT116 remarkably in a dosedependent manner. Moreover, G2-treatment led to S and G2/M phase arrest in both cells, which could be elucidated by the change of mRNA levels of p21, p27 and Cyclin E and the increased protein level of p21. G2 also induced dramatically ROS accumulated and MMP decreased, which contributed to the apoptosis through activation of both the extrinsic and intrinsic pathways via changing the genes and proteins expression involved in apoptosis pathway in both of HepG2 and HCT116 cells.

Conclusion: These findings suggested that the apoptosis in both cell lines induced by G2 was related to the extrinsic and intrinsic pathways.

Keywords: Anticancer effect, apoptosis, camptothecin-bile acid analogue, cell cycle arrest, HCT116, HepG2, mechanism.

Luo HL, Chen J, Luo T, Wu FX, Liu JJ, Wang HF, et al. Downregulation of macrophage-derived T-UCR uc.306 associates with poor prognosis in hepatocellular carcinoma. Cell Physiol Biochem 2017; 42(4): 1526-39.
[] [PMID: 28723685]
Wang XJ, Liu JB, Pandey P, Fronczek FR, Doerksen RJ, Chen JB, et al. Computationally assisted assignment of the kadsuraols, a class of chemopreventive agents for the control of liver cancer. Org Lett 2018; 20(18): 5559-63.
[] [PMID: 30192555]
Zhong JC, Zhang YJ, Chen JF, Huang RY, Yang YK, Chen HX, et al. In vitro study of colon cancer cell migration using E-jet 3D printed cell culture platforms. Macromol Biosci 2018; 18(11)e1800205
[] [PMID: 30187643]
Wu KM, Ma J, Zhan YF, Liu KZ, Ye ZY, Chen JH, et al. Down-regulation of microRNA-214 contributed to the enhanced mitochondrial transcription factor A and inhibited proliferation of colorectal cancer cells. Cell Physiol Biochem 2018; 49(2): 545-54.
[] [PMID: 30157478]
Li Y, Lin JY, Ma JY, Song L, Lin HR, Chen DY, et al. Methotrexate-camptothecin prodrug nanoassemblies as a versatile nanoplatform for biomodal imaging-guided self-active targeted and synergistic chemotherapy. ACS Appl Mater Interfaces 2017; 9(40): 34650-65.
[] [PMID: 28920426]
Yu LN, Ma J, Han JC, Wang B, Chen XY, Gao CX, et al. Licochalcone B arrests cell cycle progression and induces apoptosis in human breast cancer MCF-7 cells. Recent Pat Anti-Cancer Drug Discov 2016; 11(4): 444-52.
[] [PMID: 27719653]
Yang P, Ding GB, Liu W, Fu R, Sajid A, Li Z. Tannic acid directly targets pyruvate kinase isoenzyme M2 to attenuate colon cancer cell proliferation. Food Funct 2018; 9(11): 5547-59.
[] [PMID: 30259036]
Xing H, Wang Z, Shao D, Chang ZM, Ge MF, Li L, et al. Janus nanocarriers for magnetically targeted and hyperthermia-enhanced curcumin therapy of liver cancer. RSC Advances 2018; 8(53): 30448-54.
Wall ME, Wani MC, Cook CE, Palmer KH, McPhail AT, Sim GA. Plant antitumor agents. I. Isolation and structure of camtothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. J Am Chem Soc 1966; 88(16): 3888-901.
Hsiang YH, Hertzberg R, Hecht S, Liu LF. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 1985; 260(27): 14873-8.
[PMID: 2997227]
Hertzberg RP, Busby RW, Caranfa MJ, Holden KG, Johnson RK, Hecht SM, et al. Irreversible trapping of the DNA-topoisomerase I covalent complex: Affinity labeling of the camptothecin binding site. J Biol Chem 1990; 265(31): 19287-95.
[PMID: 2172250]
Pommier Y, Kohlhagen G, Kohn KW, Leteurtre F, Wani MC, Wall ME. Interaction of an alkylating camptothecin derivative with a DNA base at topoisomerase I-DNA cleavage sites. Proc Natl Acad Sci USA 1995; 92(19): 8861-5.
[] [PMID: 7568032]
Schluep T, Hwang J, Cheng J, Heidel JD, Bartlett DW, Hollister B, et al. Preclinical efficacy of the camptothecin-polymer conjugate IT-101 in multiple cancer models. Clin Cancer Res 2006; 12(5): 1606-14.
[] [PMID: 16533788]
Yurkovetskiy AV, Yin M, Bodyak N, Stevenson CA, Thomas JD, Hammond CE, et al. A polymer-based antibody-vinca drug conjugate platform: Characterization and preclinical efficacy. Cancer Res 2015; 75(16): 3365-72.
[] [PMID: 26113086]
Li QY, Zu YG, Shi RZ, Yao LP. Review camptothecin: Current perspectives. Curr Med Chem 2006; 13(17): 2021-39.
[] [PMID: 16842195]
Bomgaars L, Berg SL, Blaney SM. The development of camptothecin analogs in childhood cancers. Oncologist 2001; 6(6): 506-16.
[] [PMID: 11743213]
Hertzberg RP, Caranfa MJ, Holden KG, Jakas DR, Gallagher G, Mattern MR, et al. Modification of the hydroxy lactone ring of camptothecin: Inhibition of mammalian topoisomerase I and biological activity. J Med Chem 1989; 32(3): 715-20.
[] [PMID: 2537428]
Burke TG, Mi Z. The structural basis of camptothecin interactions with human serum albumin: Impact on drug stability. J Med Chem 1994; 37(1): 40-6.
[] [PMID: 8289200]
Dancey J, Eisenhauer EA. Current perspectives on camptothecins in cancer treatment. Br J Cancer 1996; 74(3): 327-38.
[] [PMID: 8695345]
Burke TG. Chemistry of the camptothecins in the bloodstream: Drug stabilization and optimization of activity. Ann N Y Acad Sci 1996; 803: 29-31.
[] [PMID: 8993497]
Leu YL, Chen CS, Wu YJ, Chern JW. Benzyl ether-linked glucuronide derivative of 10-hydroxycamptothecin designed for selective camptothecin-based anticancer therapy. J Med Chem 2008; 51(6): 1740-6.
[] [PMID: 18318465]
Guo Z, Zhou X, Xu M, Tian H, Chen X, Chen M. Dimeric camptothecin-loaded RGD-modified targeted cationic polypeptide-based micelles with high drug loading capacity and redox-responsive drug release capability. Biomater Sci 2017; 5(12): 2501-10.
[] [PMID: 29119997]
Fang S, Hou YP, Ling LB, Wang DQ, Ismail M, Du YW, et al. Dimeric camptothecin derived phospholipid assembled liposomes with high drug loading for cancer therapy. Colloids Surf B Biointerfaces 2018; 166: 235-44.
[] [PMID: 29604567]
Pan PC, Chen JA, Li XJ, Li MY, Yu HD, Zhao JJ, et al. Structure-based drug design and identification of H2O-soluble and low toxic hexacyclic camptothecin derivatives with improved efficacy in both cancer and lethal inflammation models in vivo. J Med Chem 2018; 61(19): 8613-24.
[] [PMID: 30227711]
Du HZ, Huang Y, Hou XY, Quan XP, Jiang JW, Wei XH, et al. Two novel camptothecin derivatives inhibit colorectal cancer proliferation via induction of cell cycle arrest and apoptosis in vitro and in vivo. Eur J Pharm Sci 2018; 123: 546-59.
[] [PMID: 30118848]
Zhou Y, Zhao HY, Jiang D, Wang LY, Xiang C, Wen SP, et al. Low toxic and high soluble camptothecin derivative 2-47 effectively induces apoptosis of tumor cells in vitro. Biochem Biophys Res Commun 2016; 472(3): 477-81.
[] [PMID: 26879138]
Okazaki M, Maruyama S, Masuda A, Yamamoto K. Camptothecin derivative- and HSP90 inhibitor-bonded polymers, and antitumor agents containing them WO2015125640. (2015).
Wang WC, Xia LH, Huang WW, Huang Y, Zhao XJ, Li QY, et al. Camptothecin derivative, its preparation method and application CN108484623. (2018).
Wang W, Guo WY, Zhang L, et al. Injection containing camptothecin derivative, and injection liquid, preparation and use thereof WO2017045603. (2017).
Langecker P, Steiert M, Hino T, Scicinksi J, Paulvannan K. Camptothecin derivatives and uses thereof WO2017156183. (2017).
Verma RP, Hansch C. Camptothecins: A SAR/QSAR study. Chem Rev 2009; 109(1): 213-35.
[] [PMID: 19099450]
Amin A, Bourget P, Ader F, Vidal F, Neuzillet C, Baillet-Guffroy A. Contribution and limits of a non-intrusive Raman spectroscopic method compared with HPLC for routine application to pre-delivery analytical control of two major camptothecin analogs: irinotecan and topotecan. J Raman Spectrosc 2015; 46(12): 1283-90.
Rodriguez-Galindo C, Crews KR, Stewart CF, Furman W, Panetta JC, Daw NC, et al. Phase I study of the combination of topotecan and irinotecan in children with refractory solid tumors. Cancer Chemother Pharmacol 2006; 57(1): 15-24.
[] [PMID: 16001174]
Khadka DB, Cho WJ. Topoisomerase inhibitors as anticancer agents: A patent update. Expert Opin Ther Pat 2013; 23(8): 1033-56.
[] [PMID: 23611704]
Beretta GL, Gatti L, Perego P, Zaffaroni N. Camptothecin resistance in cancer: Insights into the molecular mechanisms of a DNA-damaging drug. Curr Med Chem 2013; 20(12): 1541-65.
Park SH, Cho EK, Kim Y, Kyung SY, An CH, Lee SP, et al. Salvage treatment with topotecan in patients with irinotecan-refractory small cell lung cancer. Cancer Chemother Pharmacol 2008; 62(6): 1009-14.
[] [PMID: 18259751]
Lian QS, Xu J, Yan SS, Huang M, Ding HH, Sun XY, et al. Chemotherapy-induced intestinal inflammatory responses are mediated by exosome secretion of double-strand DNA via AIM2 inflammasome activation. Cell Res 2017; 27(6): 784-800.
[] [PMID: 28409562]
Dawson PA. Role of the intestinal bile acid transporters in bile acid and drug disposition. Handb Exp Pharmacol 2011; 201(201): 169-203.
[] [PMID: 21103970]
Li Y, Zhu CY. Enhanced hepatic-targeted delivery via oral administration using nanoliposomes functionalized with a novel DSPE-PEG-cholic acid conjugate. RSC Advances 2016; 6(33): 28110-20.
Kolhatkar V, Polli JE. Structural requirements of bile acid transporters: C-3 and C-7 modifications of steroidal hydroxyl groups. Eur J Pharm Sci 2012; 46(1-2): 86-99.
[] [PMID: 22387310]
Koji M, Yasutoshi Y, Shin-Ichi C, Hirofumi F, Tsuyoshi S, Hiroyuki M, et al. Homologue gene of bile acid transporters NTCP, ASBT, and OST-alpha in rainbow trout Oncorhynchus mykiss: Tissue expression, effect of fasting, and response to bile acid administration. Fish Physiol Biochem 2014; 40(2): 511-25.
[] [PMID: 24026769]
Moscovitz JE, Kong B, Buckley K, Buckley B, Guo GL, Aleksunes LM. Restoration of enterohepatic bile acid pathways in pregnant mice following short term activation of Fxr by GW4064. Toxicol Appl Pharmacol 2016; 310: 60-7.
[] [PMID: 27609522]
Avinash B. Conjugated anti-proliferative drug nano-particles and process for preparation thereof WO2017221270. (2017).
Zhou F, Han J, Fu JJ, Fei YY, Zhang Y. Bile acid-Xenopus laevis glucagon-like peptide-1 conjugate peptide and application thereof CN107698677. (2018).
Vivian D, Polli JE. Synthesis and in vitro evaluation of bile acid prodrugs of floxuridine to target the liver. Int J Pharm 2014; 475(1-2): 597-604.
[] [PMID: 25219859]
Zhang D, Li D, Shang L, He Z, Sun J. Transporter-targeted cholic acid-cytarabine conjugates for improved oral absorption. Int J Pharm 2016; 511(1): 161-9.
[] [PMID: 27377011]
Zhang Z, Li H, Xu G, Yao P. Liver-targeted delivery of insulin-loaded nanoparticles via enterohepatic circulation of bile acids. Drug Deliv 2018; 25(1): 1224-33.
[] [PMID: 29791242]
Zhang J, Yu C, Jiang G. Synthesis of cholic-acid-carrying polymer and in vitro evaluation of hepatoma-targeting nanoparticles decorated with the polymer. J Biomater Sci Polym Ed 2016; 27(9): 865-79.
[] [PMID: 27045998]
Gaowa A, Horibe T, Kohno M, Kawakami K. Bile acid as an effective absorption enhancer for oral delivery of epidermal growth factor receptor-targeted hybrid peptide. J Pharm Sci 2018; 107(5): 1322-9.
[] [PMID: 29273347]
Mathavan S, Chen-Tan N, Arfuso F, Al-Salami H. The role of the bile acid chenodeoxycholic acid in the targeted oral delivery of the anti-diabetic drug gliclazide, and its applications in type 1 diabetes. Artif Cells Nanomed Biotechnol 2016; 44(6): 1508-19.
[] [PMID: 26212118]
Kim KS, Kwag DS, Hwang HS, Lee ES, Bae YH. Immense insulin intestinal uptake and lymphatic transport using bile acid conjugated partially uncapped liposome. Mol Pharm 2018; 15(10): 4756-63.
[] [PMID: 30125508]
Li XN, Zhao TF, Cheng DP, Chu C, Tong SQ, Li QY, et al. Synthesis and biological activity of some bile acid-based camptothecin analogues. Molecules 2014; 19(3): 3761-76.
[] [PMID: 24662087]
Li QY, Gao Y, Qiu W, Zu YG, Su L, He WN, et al. Synthesis and anti-tumour activity of novel camptothecin-bile acid analogues. analogues. Lett Drug Des Discov 2011; 8(8): 698-703.
Li QY, Zhao TF, Zu YG, et al. Camptothecin 20-position bile acid derivative and preparation method thereof CN102516347. (2012).
Li QY, Zhang BY, Zhao TF, et al. Camptothecin 20-position bile acid derivative and preparation method thereof CN102492010. (2012).
Li QY, Zu YG, Zhao TF, et al. Camptothecin 10-position bile acid derivative and preparation method thereof CN102532237. (2012).
Li QY, Gao Y, Zu YG, et al. Camptothecin 10-position bile acid derivative and preparation method thereof CN101967172. (2011).
Xiao L, Yu E, Yue H, Li Q. Enhanced liver targeting of camptothecin via conjugation with deoxycholic acid. Molecules 2019; 24(6): 1179.
[] [PMID: 30917485]
Xiao L, Zhou Y, Zhang X, Ding Y, Li Q. Transporter-targeted bile acid-camptothecin conjugate for improved oral absorption. Chem Pharm Bull (Tokyo) 2019; 67(10): 1082-7.
[] [PMID: 31391385]
Leow CC, Dimasi N, Coffman K, et al. Preparation of bispecific anti-human VEGF-A and angiopoietin 2 antibodies for reduction of angiogenesis and therapy of cancer with reduced thromboembolic and/or renal toxicity WO2018037000. (2018).
Bicknell R, Khan KA. Modulators of the interaction of CD248 with its ligand multimerin 2 (MMRN2) for use as angiogenesis modulators and anticancer WO2018154307. (2018).
Crunkhorn S. Anticancer drugs: Tumour-specific angiogenesis inhibition. Nat Rev Drug Discov 2016; 15(5): 310.
[PMID: 27139997]
Bumcrot D, Toudjarska I, Sah DW. Lipid formulated compositions and methods for inhibiting expression of EG5 and VEGF genes WO2011034798. (2011).
Sousa JB, Fresco P, Diniz C, Goncalves J. Adenosine receptor ligands on cancer therapy: A review of patent literature. Recent Pat Anti-Cancer Drug Discov 2018; 13(1): 40-69.
[] [PMID: 29119938]
Ichim CV. Methods and compositions for treatment of cancer by inhibition of NR2F2 US20150297627. (2015).
Pentimalli F, Forte IM, Esposito L, Indovina P, Iannuzzi CA, Alfano L, et al. RBL2/p130 is a direct AKT target and is required to induce apoptosis upon AKT inhibition in lung cancer and mesothelioma cell lines. Oncogene 2018; 37(27): 3657-71.
[] [PMID: 29606701]
Salcedo TW, Rosen CA, Albert VR, Humphreys R, Vaughan T. Antibodies that immunospecifically bind to TRAIL receptor TR7 for cancer diagnosis and therapy US20050214207. (2005).
Baylin SB, Pardoll DM, Topalian SL. Cancer therapy via a combination of epigenetic modulation and immune modulation WO2015035112. (2015).
Fletcher R, Wang YJ, Schoen RE, Finn OJ, Yu J, Zhang L. Colorectal cancer prevention: Immune modulation taking the stage. Biochim Biophys Acta Rev Cancer 2018; 1869(2): 138-48.
[] [PMID: 29391185]
Iurescia S, Fioretti D, Rinaldi M. Nucleic acid sensing machinery: Targeting innate immune system for cancer therapy. Recent Patents Anticancer Drug Discov 2018; 13(1): 2-17.
[] [PMID: 29086701]
Zhang HP, Liu JR, Li GD, Wei JF, Chen HS, Zhang CP, et al. Fresh red raspberry phytochemicals suppress the growth of hepatocellular carcinoma cells by PTEN/AKT pathway. Int J Biochem Cell Biol 2018; 104: 55-65.
[] [PMID: 30195065]
Qian YY, Liu ZS, Zhang Z, Levenson AS, Li K. Pterostilbene increases PTEN expression through the targeted downregulation of microRNA-19a in hepatocellular carcinoma. Mol Med Rep 2018; 17(4): 5193-201.
[] [PMID: 29393488]
Ou W, Lv J, Zou XH, Yao Y, Wu JL, Yang J, et al. Propofol inhibits hepatocellular carcinoma growth and invasion through the HMGA2-mediated Wnt/β-catenin pathway. Exp Ther Med 2017; 13(5): 2501-6.
[] [PMID: 28565871]
Ye RF, Dai NG, He QK, Guo PY, Xiang YK, Zhang Q, et al. Comprehensive anti-tumor effect of Brusatol through inhibition of cell viability and promotion of apoptosis caused by autophagy via the PI3K/Akt/mTOR pathway in hepatocellular carcinoma. Biomed Pharmacother 2018; 105: 962-73.
[] [PMID: 30021391]
Roskoski R Jr. Targeting oncogenic Raf protein-serine/threonine kinases in human cancers. Pharmacol Res 2018; 135: 239-58.
[] [PMID: 30118796]
Li L, Zhao GD, Shi Z, Qi LL, Zhou LY, Fu ZX. The Ras/Raf/MEK/ERK signaling pathway and its role in the occurrence and development of HCC. Oncol Lett 2016; 12(5): 3045-50.
[] [PMID: 27899961]
Sidera K, Patsavoudi E. HSP90 inhibitors: Current development and potential in cancer therapy. Recent Pat Anti-Cancer Drug Discov 2014; 9(1): 1-20.
[] [PMID: 23312026]
Ren Y, Tao J, Jiang Z, Guo D, Tang J. Pimozide suppresses colorectal cancer via inhibition of Wnt/β-catenin signaling pathway. Life Sci 2018; 209: 267-73.
[] [PMID: 30107167]
Klose J, Eissele J, Volz C, Schmitt S, Ritter A, Ying S, et al. Salinomycin inhibits metastatic colorectal cancer growth and interferes with Wnt/β-catenin signaling in CD133+ human colorectal cancer cells. BMC Cancer 2016; 16(1): 896.
[] [PMID: 27855654]
Reabroi S, Chairoungdua A, Saengsawang W, Saeeng R, Kasemsuk T, Zhu WM, et al. A silyl andrographolide analogue suppresses Wnt/β-catenin signaling pathway in colon cancer. Biomed Pharmacother 2018; 101: 414-21.
[] [PMID: 29501763]
Shirley S, Morizot A, Micheau O. Regulating TRAIL receptor-induced cell death at the membrane: A deadly discussion. Recent Pat Anti-Cancer Drug Discov 2011; 6(3): 311-23.
[] [PMID: 21756247]
Peng Y, Qiu L, Xu D, Zhang L, Yu HX, Ding YD, et al. M4IDP, a zoledronic acid derivative, induces G1 arrest, apoptosis and autophagy in HCT116 colon carcinoma cells via blocking PI3K/Akt/mTOR pathway. Life Sci 2017; 185: 63-72.
[] [PMID: 28751160]
Amerizadeh F, Hassanian SM, Fiuji H, Nosrati-Tirkani A, Ghayour- Mobarhan M, Khazaei M, et al. Crocin synergistically enhances the antiproliferative activity of 5-flurouracil through Wnt/PI3K pathway in a mouse model of colitis-associated colorectal cancer. J Cell Biochem 2018; 119(12): 10250-61.
[] [PMID: 30129057]
Ni XF, Chen JJ, Lu FY, Yuan ZZ, Xu XF, Hu Z, et al. Anti-cancer effect of α-solanine by down-regulating S100P expression in colorectal cancer cells. Recent Pat Anti-Cancer Drug Discov 2018; 13(2): 240-7.
[] [PMID: 29600769]
Li Y, Lin JY, Ma JY, Song L, Lin HR, Tang B, et al. Methotrexate- camptothecin prodrug nanoassemblies as a versatile nanoplatform for biomodal imaging-guided self-active targeted and synergisticchemotherapy. ACS Appl Mater Interfaces 2017; 9(40): 34650-65.
[] [PMID: 28920426]
Wang H, Ao M, Wu J, Yu L. TNFα and Fas/FasL pathways are involved in 9-methoxycamptothecin-induced apoptosis in cancer cells with oxidative stress and G2/M cell cycle arrest. Food Chem Toxicol 2013; 55: 396-410.
[] [PMID: 23369935]
Zeng Z, Shen ZL, Zhai S, Xu JL, Liang H, Li QY, et al. Transport of curcumin derivatives in Caco-2 cell monolayers. Eur J Pharm Biopharm 2017; 117: 123-31.
[] [PMID: 28396278]
Solano ME, Thiele K, Kowal MK, Arck PC. Identification of suitable reference genes in the mouse placenta. Placenta 2016; 39: 7-15.
[] [PMID: 26992668]
Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 2016; 1863(12): 2977-92.
[] [PMID: 27646922]
Molkentin JD. Calcineurin, mitochondrial membrane potential, and cardiomyocyte apoptosis. Circ Res 2001; 88(12): 1220-2.
[] [PMID: 11420294]
Indran IR, Tufo G, Pervaiz S, Brenner C. Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. Biochim Biophys Acta 2011; 1807(6): 735-45.
[] [PMID: 21453675]
Ping YH, Lee HC, Lee JY, Wu PH, Ho LK, Chi CW, et al. Anticancer effects of low-dose 10-hydroxycamptothecin in human colon cancer. Oncol Rep 2006; 15(5): 1273-9.
[] [PMID: 16596197]
Calejo AI, Reverendo M, Silva VS, Pereira PM, Santos MAS, Zorec R, et al. Differences in the expression pattern of HCN isoforms among mammalian tissues: Sources and implications. Mol Biol Rep 2014; 41(1): 297-307.
[] [PMID: 24234751]
Fisher GA, Kuo T, Ramsey M, Schwartz E, Rouse RV, Cho CD, et al. A Phase II study of gefitinib, 5-fluorouracil, leucovorin, and oxaliplatin in previously untreated patients with metastatic colorectal cancer. Clin Cancer Res 2008; 14(21): 7074-9.
[] [PMID: 18981005]
Mullany LE, Herrick JS, Wolff RK, Slattery ML, Sakoda LC, Samowitz W, et al. miRNA involvement in cell cycle regulation in colorectal cancer cases. Genes Cancer 2018; 9(1-2): 53-65.
[PMID: 29725503]
Lansiaux A, Leonce S, Kraus-Berthier L, Bal-Mahieu C, Mazinghien R, Didier S, et al. Novel stable camptothecin derivatives replacing the E-ring lactone by a ketone function are potent inhibitors of topoisomerase I and promising antitumor drugs. Mol Pharmacol 2007; 72(2): 311-9.
[] [PMID: 17494837]
D’Arpa P, Beardmore C, Liu LF. Involvement of nucleic acid synthesis in cell killing mechanisms of topoisomerase poisons. Cancer Res 1990; 50(21): 6919-24.
[PMID: 1698546]
Kolupaeva V, Basilico C. Overexpression of cyclin E/CDK2 complexes overcomes FGF-induced cell cycle arrest in the presence of hypophosphorylated Rb proteins. Cell Cycle 2012; 11(13): 2557-66.
[] [PMID: 22713240]
Drullion C, Tregoat C, Lagarde V, Tan S, Gioia R, Priault M, et al. Apoptosis and autophagy have opposite roles on imatinib-induced K562 leukemia cell senescence. Cell Death Dis 2012; 3e373
[] [PMID: 22898871]
Baig S, Seevasant I, Mohamad J, Mukheem A, Huri HZ, Kamarul T. Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand? Cell Death Dis 2016; 7e2058
[] [PMID: 26775709]
Elmore S. Apoptosis: A review of programmed cell death. Toxicol Pathol 2007; 35(4): 495-516.
Fleury C, Mignotte B, Vayssière JL. Mitochondrial reactive oxygen species in cell death signaling. Biochimie 2002; 84(2-3): 131-41.
[] [PMID: 12022944]
Wang X. The expanding role of mitochondria in apoptosis. Genes Dev 2001; 15(22): 2922-33.
[PMID: 11711427]
Saber A, Alipour B, Faghfoori Z, Yari Khosroushahi A. Secretion metabolites of dairy Kluyveromyces marxianus AS41 isolated asprobiotic, induces apoptosis in different human cancer cell linesand exhibit anti-pathogenic effects. J Funct Foods 2017; 34: 408-21.
Chan SH, Liang PH, Guh JH. An integrated approach to elucidate signaling pathways of dioscin-induced apoptosis, energy metabolism and differentiation in acute myeloid leukemia. N-S Arch Pharmacol 2018; 391(6): 587-602.
[] [PMID: 29594316]
Liesche C, Venkatraman L, Aschenbrenner S, et al. Death receptor-based enrichment of Cas9-expressing cells. BMC Biotechnol 2016; 16(17): 1-13.
[] [PMID: 26883910]
Quisbert-Valenzuela EO, Calaf GM. Apoptotic effect of noscapine in breast cancer cell lines. Int J Oncol 2016; 48(6): 2666-74.
[] [PMID: 27081867]
Ashkenazi A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2002; 2(6): 420-30.
[] [PMID: 12189384]
Elkin ER, Harris SM, Loch-Caruso R. Trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine induces lipid peroxidation-associated apoptosis via the intrinsic and extrinsic apoptosis pathways in a first-trimester placental cell line. Toxicol Appl Pharmacol 2018; 338: 30-42.
[] [PMID: 29129777]
Chang HY, Yang X. Proteases for cell suicide: Functions and regulation of caspases. Microbiol Mol Biol Rev 2000; 64(4): 821-46.
[] [PMID: 11104820]

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Year: 2019
Page: [370 - 382]
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DOI: 10.2174/1574892814666191016162346
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